Sarcomas are a heterogeneous group of tumors that show only moderate response to treatment. In this proposal, we build on our previous work using Positron Emission Tomography (PET) to contribute to the management of sarcoma patients. These studies are also a model for PET applications in other types of cancer. The specific aims in this proposal address three important areas where we will explore PET contributions to the treatment and evaluation of a patient with sarcoma. Using [F- 18]fluorodeoxyglucose (FDG) and PET, we will perform semi-quantitative imaging studies on patients to determine tumor metabolism. This baseline patient data will be correlated with patient outcome. This work will continue our evaluation of the ability for FDG PET derived tumor measures to assess and predict time to local tumor recurrence, metastasis, and death. Rigorous methods will be applied to determine the statistical significance of the differences between survival curves. Additionally, measures of tumor heterogeneity in FDG metabolism using specialized statistical image analysis techniques will also be correlated for their ability to predict tumor response and overall survival. In another specific aim, [C- 11 ]thymidine will be implemented as a direct measure of tumor proliferation to be predictive of chemotherapy response in patients receiving neoadjuvant chemotherapy for high grade sarcomas. The [C- 11]thymidine data will be compared directly to the clinical reports of percent tumor viability' at the time of resection following neoadjuvant chemotherapy. Another subgroup of sarcoma patients under study are those patients who undergo bone allograft placement in limb salvage surgery, for treatment of bony sarcomas. At the sites of union between graft and native bone, dense bony callous forms. However, the natural history of bone allograft healing and incorporation with respect to this callous is unclear. We hypothesize that the [F-18] PET bone scans will be sensitive for characterizing the normal allograft union process and can distinguish the pathological situations of graft nonunion versus tumor recurrence in this setting. The focus of these studies are to exploit the quantitative data and high level of spatial sensitivity in PET images to characterize tissue metabolism in specific situations facing sarcoma patients. These studies also serve as a model for study in other types of cancer.